This project aims to develop zebrafish models of leukemia and sarcoma by creating transgenic zebrafish expressing know leukemia and sarcoma fusion cDNAs. These transgenic fish can then be used to identify collaborating genes required for development of the malignant phenotype. We have now generated transgenic zebrafish expressing the human TEL-AML1 translocation which is associated with pre-B-cell acute lymphoblastic leukemia. These fish have an incidence of leukemia of approximately 2%. These fish are currently being characterized and will be used for mutagenesis studies to identify the additional genetic hits required for leukemic transfomration. We are also generating transgenic zebrafish expressing the zebrafish EWS-FLI-1 translocation associated with human Ewing's sarcoma.